The polyamines, spermidine (spd) and spermine (sp), and the diamine, putrescine (pu) (called a polyamine for simplicity) may be required to maintain the structure and/or function of nucleic acids; therefore, the control of their synthesis assumes great importance. Ornithine decarboxylase (ODC) is an important control point for polyamine biosynthesis through pu. Putrescine is: the fundamental unit of spd and sp; an activator of S-adenoyl-L-methionine decarboxylase which provides the donator of propylamine residues for spd and sp synthesis; and pu is a competitive inhibitor of spermine synthase. The molecular events that control ODC are unclear, although available information hints that they act through changes in both the rates of synthesis and degradation of the enzyme. The regulation of ODC in tumor cells has received almost no attention. The long term goals of the proposed research project are to elucidate the mechanisms by which ODC is regulated in normal and cancer cells and to purify and characterize for the first time, ODC from a tumor using simian adenovirus 7-induced hamster brain tumor (HBT) as a model. Specifically, we propose to investigate: the ODC activity and the content of pu, spd, and sp of high density, nongrowing HBT cell cultures upon addition of fresh medium, which stimulates growth; the mechanism of ODC control in HBT cells in cell culture using neutral amino acids and inhibitors of protein and nucleic acid synthesis; purify the ODC from HBT cells grown in hamsters and study its enzymology in comparison to that of neonatal hamster brain. Such fundamental information is necessary for a logical approach to the development of useful anticancer drugs, and for a more rational approach to the elucidation of the functional significance of the polyamines.